Abstract
Aims/hypothesisThe aim of this study was to investigate the effect of childhood-onset type 1 diabetes on the risk of subsequent neurodevelopmental disorders, and the role of glycaemic control in this association. We hypothesised that individuals with poor glycaemic control may be at a higher risk of neurodevelopmental disorders compared with the general population, as well as compared with individuals with type 1 diabetes with adequate glycaemic control.MethodsThis Swedish population-based cohort study was conducted using data from health registers from 1973 to 2013. We identified 8430 patients with childhood-onset type 1 diabetes (diagnosed before age 18 years) with a median age of diabetes onset of 9.6 (IQR 5.9–12.9) and 84,300 reference individuals from the general population, matched for sex, birth year and birth county. Cox models were used to estimate the effect of HbA1c on the risk of subsequent neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability.ResultsDuring a median follow-up period of 5.6 years, 398 (4.7%) individuals with type 1 diabetes received a diagnosis of any neurodevelopmental disorder compared with 3066 (3.6%) in the general population, corresponding to an adjusted HR (HRadjusted) of 1.31 (95% CI 1.18, 1.46) after additionally adjusting for other psychiatric morbidity prior to inclusion, parental psychiatric morbidity and parental highest education level. The risk of any neurodevelopmental disorder increased with HbA1c levels and the highest risk was observed in patients with mean HbA1c >8.6% (>70 mmol/mol) (HRadjusted 1.90 [95% CI 1.51, 2.37]) compared with reference individuals without type 1 diabetes. In addition, when compared with patients with diabetes with HbA1c <7.5% (<58 mmol/mol), patients with HbA1c >8.6% (>70 mmol/mol) had the highest risk of any neurodevelopmental disorder (HRadjusted 3.71 [95% CI 2.75, 5.02]) and of specific neurodevelopmental disorders including ADHD (HRadjusted 4.16 [95% CI 2.92, 5.94]), ASD (HRadjusted 2.84 [95% CI 1.52, 5.28]) and intellectual disability (HRadjusted 3.93 [95% CI 1.38, 11.22]).Conclusions/interpretationChildhood-onset type 1 diabetes is associated with an increased risk of neurodevelopmental disorders, with the highest risk seen in individuals with poor glycaemic control. Routine neurodevelopmental follow-up visits should be considered in type 1 diabetes, especially in patients with poor glycaemic control.Graphical abstract
Highlights
Type 1 diabetes is the predominant form of diabetes in childhood and is increasing worldwide [1]
We included 8430 individuals diagnosed with childhoodonset type 1 diabetes and 84,300 matched reference individuals from the general population (Fig. 1)
A Matched on sex, birth year and birth county population to patients with type 1 diabetes whose first documented HbA1c was performed within the first 3 month after diagnosis (ESM Table 6 and 7) and using International Society for Pediatric and Adolescent Diabetes (ISPAD) HbA1c cutoffs (ESM Table 8 and 9) yielded similar results. In this large population-based cohort study, we found that individuals with childhood-onset type 1 diabetes were at higher risk of neurodevelopmental disorders compared with their peers from the general population and that this risk increased at higher mean HbA1c levels
Summary
Type 1 diabetes is the predominant form of diabetes in childhood and is increasing worldwide [1]. Several studies have suggested a link between childhood-onset type 1 diabetes and increased risk of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability [2,3,4]. Statistically significant increased risk of neurodevelopmental disorders (HRs 1.5–1.7) was observed in individuals with childhood-onset type 1 diabetes, but not in their healthy siblings. This suggests that diabetesrelated factors play important roles in the aetiology of neurodevelopmental disorders in individuals with diabetes rather than shared genetic and environmental influences [2]
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